The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ]

During the trial we will measure the incidence and severity of all side effects (according to CTC version 4.0). The change in immunogenecity will be measured according to the induction of p53-specific T cells upon treatment.

This study investigates the feasibility and immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination in patients with platinum-resistant ovarian cancer.

Detailed Description

Recurrent ovarian cancer has a dismal prognosis and there is a pressing need to identify more efficient therapies. Ovarian cancer is highly immunogenic and good survival is tightly linked to the presence of tumor-infiltrating T cells and the absence of immunosuppressive immune cells. This anti-tumor immune response might be primed by chemotherapy.

Gemcitabine has immune-modulatory properties in addition to its direct cytotoxic effect in platinum resistant ovarian cancer. Additionally, Peg-Intron allows the full maturation of dendritic cells, thereby enhancing the anti-tumor response. Moreover, the tumor-associated self-antigen p53 is commonly over-expressed in ovarian cancer and can serve as a target for immunotherapy. Therefore, chemo-immunotherapy with gemcitabine and Peg-Intron plus/minus p53 SLP vaccination seems an attractive treatment for recurrent, p53+ ovarian cancer patients.

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Biological: p53 SLP

8.2.3 The p53 SLP vaccine consists of 9 synthetic 25-30 amino acids long overlapping peptides, spanning amino acids 70-235 of the wt-p53 protein (patent number WO2008147186). Peptides are prepared at the GMP facility of the Department of Clinical Pharmacy and Toxicology of the LUMC. At the day of immunization peptides (0.3 mg/peptide) were dissolved in dimethyl sulfoxide (DMSO, final concentration 20%) admixed with 20 mM phosphate buffer (pH7.5) and emulsified with an equal volume of Montanide ISA-51.The vaccine (2.7mL) is administered subcutaneously.